The goal of this proposal is to establish a large respiratory of DNA samples from 2,000 deaf probands in multiplex and simplex sibships. A sequential screening strategy will then be used to identify new genes for deafness. Candidate genes to be screened will include the human orthologs of murine genes for deafness and other members of gene families in which some are known to be the cause of deafness. The research subjects will be ascertained from an Annual National Survey of Deaf Students at Gallaudet University along with students from the University. The research will also yield important information on the distribution of mutations at currently recognized genes for syndromic and non- syndromic deafness. Using available information on relevant outcome variables such as audiograms and the use of hearing aids and cochlear implants, these data will permit a search for clinically relevant genotype-phenotype correlations. The resulting data will be used to search for ethnic differences in the frequency of genes for deafness as well as secular trends in the incidence of deafness. The frequency of common forms of deafness in multiplex and simplex sibships will be used as index traits to estimate the relative frequency of deafness in the Annual Survey population. Finally, computer modeling will be employed to explore the consequences of non-random mating among the deaf and to test the hypothesis that assortative mating has contributed to the high frequency of a common form of genetic deafness caused by mutations in the Connexin 26 gene.